Model for regulation of monomer to dimer transition by self-folding of the neck helices. When Unc104 is sparsely distributed on an organelle membrane (A), the self-folded state is favored over the unfolded state in a dynamic equilibrium. The self-folded Unc104 monomers may move very slowly and nonprocessively, like Unc104362 (Tomishige et al., 2002). These monomers may show some plus end–directed biased diffusion, but will not generate significant force against an opposing load (Okada et al., 2003). However, when Unc104 is clustered, possibly in lipid rafts, on the organelle membrane at high local concentrations (B), unfolded monomers are recruited into dimers shifting the equilibrium away from the monomeric state. The dimerized Unc104 would then undergo fast processive motility along microtubules and generate maximal force. The monomer to dimer equilibrium shift may occur in solution, but may also be favored by the presence of microtubules. Blue and red cylinders represent H1 and H2, respectively. Orange spheres represent the FHA domains. Yellow spheres represent the membrane PH domain.